In 1981, Matthew Meselson pointed out that the puzzle brought to light by Darwin, of what constitutes heredity, was solved in two tranches. The first lasted from 1900, when Mendel’s work of the last half of the nineteenth century came into the consciousness of the scientific community. It lasted until 1950 or so, when the rules of genetic inheritance had been firmly established.
We then entered a new world of molecular genetics, learning first the chemistry of the underlying molecules of inheritance. Once we knew the chemistry and the topology of the DNA molecule, we learned how to cut it and how to paste it. That resulted in the recombinant DNA revolution of the mid-1970s.
We also learned how to modify DNA in the chromosomes of experimental animals. Those methods remained cumbersome and imperfect, and extending them to human beings was initially unthinkable. Over the years, however, the unthinkable has become conceivable. Today, we sense that we are close to being able to alter human hereditary. Now we must face the questions that arise. How, if at all, do we as a society want to use this capability?
Thus, we are part of a historical process that dates from Darwin and Mendel’s work in the nineteenth century. We in the scientific community are taking on a heavy responsibility for our society because we understand that we could be on the cusp of a new era in human history. Although gene editing is in its infancy today, it is likely that the pressure to use gene editing will increase with time, and the actions we take now will guide us into the future.
We should remember that there is a larger context for our deliberations. Aldous Huxley, in his book Brave New World, imagined a society built on selection of people to fill particular roles, with environmental manipulation to control the social mobility and behavior of the population. That book was written in 1932. He couldn’t have conceived of gene editing, but the warning implicit in his book is one that we should take to heart as we face the prospect of this new and powerful means to control the nature of the human population.
Thus, we are initiating a process of taking responsibility for technology with far-ranging implications. The process of accepting this challenge began in January 2015, when concerns about the consequences of modifying human genomes prompted a small group of scientists and ethicists to convene a meeting in Napa, California. That group recognized the opportunity that genome engineering technology presented to cure genetic disease in humans. It realized that these methods provide the opportunity to reshape elements of the biosphere, providing benefit to the environment and to human society.
Although these new technologies offer unprecedented opportunities for advancing science and treating disease, the group recognized that they might be used prematurely or in ways that might be viewed as inappropriate. Because of these concerns, those at the Napa meeting offered a number of recommendations and called for an international dialogue to further consider the attendant ethical, social, and legal implications of using germline modification techniques.
The National Academies of Sciences and Medicine agreed to convene an International Summit on Human Gene Editing and asked me to chair the planning committee. When the committee began its preparations, initial deliberations focused on defining the parameters of the discussion. We recognized that the application of gene editing techniques is not limited to humans. Such technologies can and are already being used to make genetic modifications in non-human organisms. The use of gene editing technologies to alter plants and animals raises many ethical and societal issues that are in and of themselves worthy of careful consideration.
We decided that to maintain focus, to avoid the discussion becoming too diffuse, we needed to limit the conversation to when and whether to proceed with conscious modification of the human genome. We believe that the tactical, clinical, ethical, legal, and social issues relating to the potential to make genetic changes that can be passed on to future generations were sufficiently complex to be a worthy target for a three-day meeting.
The committee was also aware that there are numerous relevant concurrent projects under way, both within the U.S. National Academies and in the larger community of stakeholders. These include two U.S. National Academies studies, one on gene drive in non-human organisms and the other on genetic modification of eggs and zygotes for the prevention of mitochondrial disease.
The planning committee believed that the key was to develop an agenda that gave voice to perspectives not represented in these other activities. The organizing committee recognized from the start that modern science is a global enterprise and that gene editing technologies are available to and are in use by researchers around the world. Furthermore, different cultures are likely to approach the question of human genome editing from different perspectives. The voices of diverse cultures should be heard.
Equally important, consideration of the path forward is not solely the responsibility of scientific researchers. The conversation must incorporate a broad range of stakeholders, including individuals from the bioethics community and social science community, along with specialists in medicine, regulatory affairs, and public policy, as well as, of course, the lay public.
The Summit should be seen as an opportunity to launch a much broader public discussion. It is part of a larger effort to inform policy makers and the public about recent advances. Although powerful new gene editing technologies, such as CRISPR-Cas9, hold great promise, they also raise concerns and present complex challenges.
We are saying that this is something to which all people should pay attention. Some might consider that to be fear mongering, but we hope that most will see it as the responsible acceptance of the National Academies’ role as expert advisers to the public.
In 1975, I had the privilege of participating in the Asilomar conference on recombinant DNA. That meeting was organized to “review scientific progress in research on recombinant DNA molecules and to discuss appropriate ways to deal with the potential biohazards of this work.”
In 1975, as today, we believed that it was prudent to consider the implications of a particular remarkable achievement in science. Then, as now, we recognized that we had a responsibility to include a broad community in our discussion. A lot has changed since 1975.
Science has become an increasingly global enterprise. The public has become ever more aware of the power of science and has seen the remarkable rate of societal change that can be brought on by the application of new science.
The public has witnessed the huge benefits of basic and medical research, but it is questioning whether these benefits bring attendant modifications of nature that require controls. The public also has become more engaged in debates about science and scientific progress. The new modes of rapid communication have provided novel platforms for these discussions.
At Asilomar, the press participated with the understanding that nothing would be written about what was said until the meeting was concluded. At the Summit, individuals sent blogs, tweets, and retweets as the discussion was taking place. The entire event was webcast around the world, and the video is available online for all to see.
This Summit incorporated many themes and many perspectives, but the overriding question was when, if ever, will we want to use this gene-editing technology. When will it be safe to use it? When will it be therapeutically justified to use it? And a more difficult question, when will we be prepared to say that we are allowed to use editing for genetic enhancement purposes?
These are deep and disturbing questions, and the Summit will not be the last word on human gene editing. Rather, we hope that our discussions will serve as a foundation for a meaningful and ongoing global dialogue.
David Baltimore is president emeritus and Robert Andrews Millikan Professor of Biology at Caltech. He chaired the planning committee for the International Summit on Human Gene Editing.